Overcoming inhibition in the spindle checkpoint

Abstract

Spindle checkpoint silencing is a critical step during mitosis that initiates chromosome segregation, yet surprisingly little is known about its mechanism. Protein phosphatase I (PP1) was shown recently to be a key player in this process, and in this issue of Genes & Deverlopment, Akiyoshi and colleagues (pp. 2887-2899) identify budding yeast Fin1p as a kinetochore-localized regulator of PP1 activity toward checkpoint targets. Here we review recent mechanistic insights and propose a working model for spindle checkpoint silencing.

Figure 1.

Kinetochore-localized PP1 opposes Aurora B activity to promote anaphase onset. Aurora B regulates the metaphase–anaphase transition in at least two ways: (1) destabilization of kinetochore–microtubule connections failing to produce tension, and (2) activation of the spindle checkpoint. We propose that interaction between a kinetochore component (e.g., Spc105/KNL1) and PP1 is required to counteract both processes. However, distinct substrate-specifying regulators of PP1 oppose different Aurora B functions on kinetochores. Fin1p-associated PP1 (PP1^Fin1) opposes Aurora B action in the spindle checkpoint and promotes spindle checkpoint silencing. Another as-yet-unknown regulator of PP1 might counteract the Aurora-dependent microtubule-destabilizing activity.